The present invention relates to a vector for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells, a method for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells, uses of said vector as well as malignant B cells containing said vector.
The immunoglobulin idiotype expressed on B cell lymphomas is a tumor-specific antigen which however shows a low immunogenicity in the host bearing the tumor. Several approaches have been evaluated to induce an immune reaction against the idiotype. I. a., the idiotype has been coupled to GM-CSF to be used as a soluble protein for the vaccination of mice (Nature 362, 755-758, 1993). GM-CSF is able to recruit professional antigen-presenting cells and leads to an effective presentation of the idiotype and, thus, to the activation of T cells. This approach bears the disadvantage that the immunoglobulin V genes of the lymphoma have to be cloned and the fusion protein has to be produced in vitro and purified. Therefore, this would require in a clinical situation to prepare individual vaccines for each patient.
It is an object of the present invention to provide novel vectors which may be employed universally in patients without need to prepare individual vaccines.
This object has been solved according to the invention by means of a vector for the expression of immunoglobulin-cytskine fusion proteins in malignant B cells at least containing operably linked to each other
(a) a region of at least 1.5 kb which is homologous to a region of the xcexc intron the xcexa intron and which optionally contains or lacks or contains a non-functional Cxcexc or C78  enhancer;
(b) at least one DNA sequence encoding a domain of an immunoglobulin or a part thereof;
(c) a DNA sequence encoding a cytskine; and
(d) a marker selectable in eukaryotic B cells which optionally contains an enhancer or lacks a functional enhancer region wherein following integration the expression of this marker is controlled by the cellular Cxcexc or Cxcexa enhancer.
Preferred embodiments of the invention become obvious from the dependent claims, the following Description as well as the Example.